In the realm of pharmaceutical formulations, there is a class of drug-delivery formulations that are designed to release bioactive agents for a desired period of time following a single administration. Depot formulation is one name used to describe these long-acting formulations. Depot formulations can be fabricated in many ways. A typical formulation approach to prepare a depot formulation or implant is by manufacturing a solid matrix that includes a bioactive agent and a polymeric excipient. The purpose of the polymeric excipient of the implant is to restrict the influx of water, which in turns controls the dissolution of the bioactive agent followed by the release of the bioactive agent from the implant matrix. In addition to the physical and chemical properties of the bioactive agent, the amount of bioactive agent in the implant contributes to the rate of bioactive agent release. That is, increasing the amount of bioactive agent increases the rate of release. Unfortunately, some implant formulations require a high amount of bioactive agent inside in order to have enough bioactive agent available to achieve dose and duration requirements for a particular medical indication. A high amount of bioactive agent incorporated inside the implant, however, may cause the release the bioactive agent to occur too fast or even at an uncontrollable rate.
It is an object of the present invention to provide delivery systems with a controlled release even at high loadings. Moreover, it is an object of the present invention to provide delivery systems and methods for their manufacture having decreased microbial contamination. It is a further object of the present invention to provide delivery systems having a smooth or smoother (than untreated) surface for easy administration. It is another object of the present invention to provide delivery systems where the delivery rate can be adjusted by modifying the surface.
The present invention solves this rapid release problem, i.e., the bioactive agent being released too fast, by modifying the polymeric surface or polymer skin of a delivery system by exposing the polymer present in the system to a fluid. The fluid-treatment causes the properties of the polymer on the surface of the delivery system to change such that the system is less permeable. It is the fluid treatment of the delivery system that is responsible for the slower release of the bioactive agent from the delivery system. In addition, the delivery systems produced herein are generally smoother than other delivery systems, which can facilitate the administration of the system to the subject. Additionally, the methods described herein can lower the bioburden of the delivery system by reducing the presence of microorganisms present on the system. Finally, the delivery systems produced herein have increased tensile strength, i.e., reduced friability, which aids in the preparation and administration of the system.